• R Rossaint, K Lewandowski, and W M Zapol.
• Klinik für Anästhesiologie, Universitätsklinikum Aachen, Pauwelsstraße 30, 52074, Aachen, Germany, rrossaint@ukaachen.de.
• Intensive Care Med. 2014 Nov 1; 40 (11): 1649-58.

IntroductionMore than 20 years have passed since we reported our results of treating patients with the acute respiratory distress syndrome (ARDS) with inhaled nitric oxide (iNO). The main finding was that iNO alleviated pulmonary hypertension (PH) by selective vasodilation of pulmonary vessels in ventilated lung areas. This, in turn, improved arterial oxygenation.MethodsWe now set out to review the time span between the discovery of NO in 1987 and today in order to identify and describe interesting areas of research and clinical practice surrounding the application of iNO.Major FindingsEnhancement of ventilation-perfusion matching and alleviation of PH in ARDS, treatment of PH of the newborn, and treatment of perioperative PH in congenital heart disease serve as just a few exciting examples for the successful use of iNO. Breathing NO prevents PH induced by stored blood transfusions or sickle cell disease. Exploiting the anti-inflammatory properties of NO helps to treat malaria.DiscussionRegarding the use of iNO in ARDS, there remains the unresolved question of whether important outcome parameters can be positively influenced. At first glance, several randomized controlled trials and meta-analyses seem to send the clear message: "There is none!" Careful analyses, however, leave sufficient room for doubt that the ideal study to produce the unequivocal proof for the inability of iNO to positively impact on important outcome parameters has, as yet, not been conducted.ConclusionIn summary, the discovery of and research on the many positive effects of iNO has improved care of critically ill patients worldwide. It is a noble effort to continue on this path.

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